Role of carbon monoxide in CCK-8 ameliorating acute lung injury induced by LPS

AIM: To study the role of carbon monoxide (CO) in the mechanism of cholecystokinin-octapeptide (CCK-8) for attenuation of acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Fifty-six adult male rats were randomly divided into seven groups: control group, LPS group, LPS+ZnPP (a specific inhibitor of HO-1) group, LPS+Hemin (Hm， CO donor) group, CCK-8+LPS group, CCK-8+LPS+ZnPP group and CCK-8 group (n=8 for each). Bronchoalveolar lavage was performed 2 h, 6 h and 12 h respectively after treatments. The numbers of polymorphonuclear leukocytes (PMN) in bronchoalveolar lavage fluid (BALF) was detected. The mortality of rats and the structure of lung tissues were observed. MDA and CO contents in lung tissues were also measured. RESULTS: The mortalities of rats were both zero 2 h and 6 h after agent administration. The mortality of rats was higher than control group 12 h after LPS administration. The mortality of rats in LPS+Hm and CCK-8+LPS group were lower than that in LPS group, and its in LPS+ZnPP and CCK-8+LPS+ZnPP group were lower than that in LPS and CCK-8+LPS group, respectively. Lung injury was observed in LPS group. At the same time the number of PMN, MDA and CO content were higher than those in control group. The degree of lung injury, PMN numbers and MDA content were lower, while CO content in LPS+Hm and CCK-8+LPS group were higher than those in LPS group. However, the degree of lung injury, PMN number and MDA content were higher, CO content were lower in LPS+ZnPP and CCK-8+LPS+ZnPP group than those in LPS and CCK-8+LPS group, respectively. CONCLUSION: CCK-8 attenuates the LPS-induced acute lunginjury by means of anti-oxidation and inhibition of PMN aggregation, which are both mediated by CO.